“It Is Important That The Methodology Is Right“

Clinical Trials: “It is important that the methodology is right“

09/22/2010

Initially it is a puzzle made up of small pieces or an assumption that question established diagnostics and therapy methods. Yet not always do the individual components add up to the desired shape. Being the core of evidence-based medicine, clinical trials are admittedly indispensable for the systematic development and quality inspection of pharmaceuticals and surgical- and radiation methods.

MEDICA.de spoke with Doctor Stefan Sauerland, Head of Department for non-drug interventions at the Institute for Quality and Efficiency in Health Care (IQWiG) on how medical studies are conducted, who can author a study and what they reveal.

MEDICA.de: Doctor Sauerland, there are many different medical research studies that are, clinical trials. What characterises such a typical assessment?

Stefan Sauerland: The typical studies almost all apply to drugs. It’s a matter of treatment interventions, and correspondingly the regulations are relatively strictly worded. Generally we differentiate between three phases. In Phase I you check on test subjects as to how far a drug is actually tolerated. In Phase II typically the correct dose is determined. This is followed by Phase III, the randomized clinical trial. Here by chance some of the patients receive the new drug and the others receive the previous standard drug.

MEDICA.de: Who is authorised to conduct a clinical trial?

Sauerland: In pharmaceutical studies this is very strictly regulated. There is an obligation that in each of these studies in Germany a so-called “sponsor” must take over the overall responsibility – even if he is not necessarily contributing the money for the study. “Sponsors“ can be a multitude of organizations, individuals such as physicians, medical institutions, foundations, voluntary groups and pharmaceutical companies. In a pharmaceutical study, an ethics committee decides whether the one that wants to conduct the study and the other participants are indeed sufficiently qualified. This is dependent on the risk potential for the test persons. A very invasive and critical study is definitely not going to take place at a county hospital or at a family doctor’s office.

MEDICA.de: Keyword “sponsors.“ Should you always take a critical look at who conducts a study?

Sauerland: From our point of view it does not actually matter who conducts the study and who pays for it. It is important that the methodology is right.

MEDICA.de: Is there some type of recommendation or regulation for this?

Sauerland: This is strictly regulated for pharmaceutical studies. Every drug study must be announced to the supreme Federal authority, the “Federal Institute for Drugs and Medical Devices” (BfArM). It holds all the rains and watches over every regulation being adhered to. Additionally, the EU regulation also stipulates for instance that objectionable adverse effects of a drug must be reported. There are further laws at the federal and state level. The physician’s professional law for example determines that one needs to ask the ethics commission before beginning with a study. Generally of course you always need to ask the patient, because otherwise data protection regulation issues might occur.

Diagnostic studies mostly get by without the addition of a drug. As a rule, generally fewer regulations need to be adhered to.

MEDICA.de: Based on which criteria should clinical trials be carried out?

Sauerland: There is a whole set of criteria: scientific, ethical, organizational and legal criteria. In scientific criteria for example a comparison is the central tenet. Every time you measure something, you need a comparison. You should make sure that you do not compare apples and oranges. This leads to the fact that randomized, clinical trials in most cases stand on top of the hierarchy of evidence.

MEDICA.de: You mostly deal with non-drug, diagnostic interventions. How are these studies conducted?

Sauerland: Most studies in this field are not randomized. In the majority of cases the point is to provide evidence that a diagnostic intervention has high psychometric properties and that you can distinguish between a healthy and a sick person. Sometimes you also have a comparative test available. For example, you compare positron emission tomography to computer tomography.

In diagnostic studies you then have a reference standard, which ideally is the gold standard i.e, the best method for proof or exclusion of a disease, which every new intervention needs to measure up against. Admittedly, a true gold standard is not always available. This is due to the fact that you attain this data for instance though an autopsy or a histopathological examination. This is just not possible in many cases.

MEDICA.de: The IQWiG also furnishes opinions for external studies. Does it often occur that you have to reject a study?

Stefan Sauerland: In its assessment of medical interventions, the IQWiG always has a high percentage of primary hits in literature searches, which then need to be excluded. This is because we search very broadly, so we do not miss anything. Additionally, it is also due to the fact that most studies that are being published are often only mediocre.

MEDICA.de: Can a layperson recognize the “quality“of a study?

Sauerland: This is relatively complicated, because there are a lot of possible sources of error in a study. Above all, the criteria of evidence-based medicine must be paid attention to. You can learn how to read or interpret studies very well in courses on evidence-based medicine.

MEDICA.de: What characterizes the high quality of a study?

Sauerland: For all therapy questions you need a randomized study, preferably one that is blinded to exclude the “subconscious influence“ of data. In clinical diagnostics you ideally also have a randomized study. A blinding of the study is definitely also interesting. When you research diseases where a therapy has an impact very quickly, in individual cases it is sometimes possible to do without a randomized study. But it is always important to have a comparison group and that it is a fair comparison.

The interview was conducted by Diana Posth and translated by Elena O’MearaMEDICA.de